Is CPT2 p.Ser113= (c.339G>A) pathogenic?

CPT2 p.Ser113= (c.339G>A) is classified Uncertain significance in CPT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). Very rare (popmax 0.0033%, sas); Associated with carnitine palmitoyl transferase II deficiency, neonatal form.

How common is CPT2 p.Ser113= (c.339G>A) in the general population?

CPT2 p.Ser113= (c.339G>A) is very rare (popmax 0.0033%, sas) (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CPT2 p.Ser113=

Q: What condition is associated with CPT2 p.Ser113= (c.339G>A)?

CPT2 p.Ser113= (c.339G>A) is associated with carnitine palmitoyl transferase II deficiency, neonatal form, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.339G>A · rs778017005 · VCV651934

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Conditions

carnitine palmitoyl transferase II deficiency, neonatal form

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.93	GERP -2.5, phastCons 0.98
Overall
CADD	5.416	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/91,010 alleles

Filtering AF 0.000876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000869% 14/1,611,208 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,337
African / African-American	0.00267%	37,434
East Asian	0.00223%	44,882
Finnishnot grpmax-eligible	0.00156%	64,038
European (non-Finnish)	0.000595%	168,206

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CPT2
Protein: p.Ser113=
Coding: c.339G>A
MANE Select: NM_000098
dbSNP: rs778017005
Type: single nucleotide variant
Location: chr1:53202428 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.52
Residue 113: a UniProt-annotated variant site (in cpt2d; muscular form; frequent mutation)

Full CPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

carnitine palmitoyl transferase II deficiency, neonatal form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: carnitine palmitoyl transferase II deficiency, myopathic form carnitine palmitoyl transferase II deficiency, severe infantile form encephalopathy, acute, infection-induced, susceptibility to, 4 carnitine palmitoyltransferase II deficiency

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Ser113Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
CPT2 c.340+1G>C Pathogenic/Likely pathogenic ★★ same condition
CPT2 c.340+5G>A Likely pathogenic ★★ same condition
CPT2 c.341-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Ala67Gly Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Gln Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Ter Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg151Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cpt2-p-ser113 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown